Overall objectives are to define the factors controlling collagen and other connective tissue synthesis and degradation in man in health and in disease with particular emphasis on metabolic bone diseases and inflammatory and metabolic joint disease. In addition, we continue our investigation of the roles that humoral antibodies and delayed hypersensitivity play in these diseases and the effects of humoral mediators. The mechanism whereby drugs affect these processes is also under consideration with respect to both in vitro effects and effects in patients. We also are striving to understand the biochemistry and biology of morphogenesis concentrating on the connective tissue and to try to understand the machinery and regulatory processes involved in embryonic development, regeneration, healing and disease resulting from abnormalities in the morphogenetic processes. In addition, we are engaged in the study of the biosynthesis of the core region of glycoproteins by use of synthetic peptides and glycopeptides as acceptors and of synthetic polyprenol phosphate as activated sugar intermediates. Synthetic polyprenol sugar phosphates will also be investigated as precursors in the biosynthesis of hyaluronic acid, heparin, and heparin sulfate.